(1) Field of the Invention
This invention relates to novel mannobiose derivatives useful as a component modifying pharmaceutical preparations, such as liposomes, having a specific affinity for Kupffer cells of liver.
(2) Prior Art
Recently, organ- or cell-directed preparations have been reported in the pharmaceutical and medical fields. For example, several proposals have been made regarding a technique that a drug is selectively delivered to an objective internal organ or cells by administering the drug encapsulated in liposomes.
One such proposal is found in a report by Szoka, et al. (Biochem. Biophys. Res. Comm., 110, 140-146 (1983)) relating to a liposomal preparation of which target is macrophage cells such as Kupffer cells of the liver.
In this prior art, a fatty acid diester of dimannosylglceride is mixed with liposomal lipid membrane to give the liposomes an affinity for macrophage cells, but the above diester compound is a natural substance isolated from a luteus coccus, so it is difficult to produce the compound industrially. Further, as examples of research using a synthetic substance as a liposome lipid membrane-modifying substance for targeting macrophage cells, typically Kupffer cells of liver, a report by Bachhawat et al. (Biochim. cells of liver, a report by Shen et al. (Biochim. Biophys. Acta, 632, 562-572 (1980)), a report by Shen et. al. (Biochim. Biophys. Acta, 674, 19-29 (1981)), are shown. In the former, a substance obtained by coupling (i) p-aminophenyl-D-mannoside obtained by reduction of p-nitrophenyl-D-mannoside, (ii) phosphatidylethanolamine which is too expensive to obtain as a pure product among natural phospholipids and (iii) glutaraldehyde is used. In the latter report, a compound obtained by linking a hexyl group (--(CH.sub.2).sub.6 --) to a hydroxyl group at the 3-position of cholesterol and further linking the resulting hexyl group to the C1-position of D-mannose through thio group (--S--) is used. Thus, in both methods, compounds having a complicated structure are used and are not useful in view of industrial production, safety after administration to living bodies or the like.
As is seen from the foregoing, though liposomal preparations of which target is macrophage cells, typically Kupffer cells of the liver, have been prepared, the objective efficiency for the targetting and industrial production have not been attained.